Dapagliflozin also helped some patients lose weight; two patients developed ketones

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Hemoglobin A1C -- patients' average blood glucose over a 90-day period -- declined by .66 percent among participants who received the triple therapy.

BUFFALO, N.Y. – University at Buffalo endocrinologists who
in recent years found that patients with Type 1 diabetes benefit
from insulin plus a drug designed for Type 2 diabetes, have now
found that they also can benefit from dapagliflozin, another drug
designed and marketed to treat Type 2 diabetes.

On Aug. 4, researchers at the Jacobs School of Medicine and
Biomedical Sciences at UB published a paper online
ahead of print in the Journal of Clinical Endocrinology and
Metabolism that reports that patients with Type 1 diabetes saw
improved blood glucose control with a “triple therapy”
that included insulin, liraglutide and dapagliflozin.

Paresh Dandona, MD, PhD, senior author on the paper, is SUNY
Distinguished Professor and chief of endocrinology, diabetes and
metabolism in the Department of Medicine in the Jacobs School of
Medicine and Biomedical Sciences. He sees patients through UBMD
Internal Medicine at the Diabetes and Endocrinology Center of
Western New York, where the study was conducted.

Thirty people who had Type 1 diabetes participated in the
randomized, placebo-controlled clinical trial. Participants were
between the ages of 18 and 75, and were already taking liraglutide
and insulin to manage their diabetes. Twenty participants were
randomly assigned to receive 10 milligrams of dapagliflozin daily
for 12 weeks, and the other 10 received a placebo during that
period.

“Since liraglutide produces improvements most
impressively in patients with higher body mass index and higher
hemoglobin A1C, it is clear that we need other agents that act
independently of insulin since Type 1 diabetics have no beta cells
that produce insulin,” Dandona explained.

Hemoglobin A1C – patients’ average blood glucose
over a 90-day period – declined by 0.66 percent among
participants who received the triple therapy, while there was no
significant change in the placebo group. Fourteen of the 17 people
on the triple therapy lost weight, with weight loss averaging four
pounds. Patients in the placebo group did not lose weight.

Twenty-six participants completed the study. Two of the
participants receiving the triple therapy developed diabetic
ketoacidosis, a dangerous complication that occurs when acids and
substances called ketones build up in the blood due to lack of
insulin. This occurred within two days of researchers increasing
the daily dapagliflozin dose to 10 milligrams from 5 milligrams.
Both people were withdrawn from the study.

“Our data also show for the first time that all patients
on dapagliflozin experience an increase in ketones,” Dandona
said. “This may predispose people to developing diabetic
ketoacidosis, particularly among those who have a marked reduction
in insulin from taking liraglutide together with dapagliflozin and
who have consumed too few carbohydrates. Our study sheds light on
potential strategies for preventing diabetic ketoacidosis, but more
research is still needed in this area.”

Dandona said that these data suggest that insulin dose
reductions should be minimized and that the higher dose of
dapagliflozin should not be used in such patients.